Alzheimer's Mechanisms in Ischemic Brain Degeneration

Abstract

There is increasing evidence for influence of Alzheimer's proteins and neuropathology on ischemic brain injury. This review investigates the relationships between b-amyloid peptide, apolipoproteins, presenilins, tau protein, a-synuclein, inflammation factors, and neuronal survival/ death decisions in brain following ischemic episode. The interactions of these molecules and influence on b-amyloid peptide synthesis and contribution to ischemic brain degeneration and finally to dementia are reviewed. Generation and deposition of b-amyloid peptide and tau protein pathology are important key players involved in mechanisms in ischemic neurodegeneration as well as in Alzheimer's disease. Current evidence suggests that inflammatory process represents next component, which significantly contribute to degeneration progression. Although inflammation was initially thought to arise secondary to ischemic neurodegeneration, recent studies present that inflammatory mediators may stimulate amyloid precursor protein metabolism by upregulation of b-secretase and therefore are able to establish a vicious cycle. Functional brain recovery after ischemic lesion was delayed and incomplete by an injuryrelated increase in the amount of the neurotoxic C-terminal of amyloid precursor protein and b-amyloid peptide. Moreover, ischemic neurodegeneration is strongly accelerated with aging, too. New therapeutic alternatives targeting these proteins and repairing related neuronal changes are under development for the treatment of ischemic brain consequences including memory loss prevention.

Review paper Neurogenesis and neuroprotection in postischemic brain neurodegeneration with Alzheimer phenotype: is there a role for curcumin?

“…One of the earliest affected brain structures in brain ischemia is the hippocampus, which is involved in the formation and consolidation of memory [46,53]. The subgranular zone of the hippocampus dentate gyrus constitutes one of the only two neurogenic zones of the mature brain.…”

“…Cognitive deficits after ischemia can be attributed to damage to certain vulnerable brain regions including the hippocampus [47] and temporal cortex [42], as well as sub-cortical white matter tracts [44,45]. The hippocampus, which is crucial for declarative memory formation, demonstrates atrophy [43,46,47]. Postischemic dementia is one of the main causes of dependency in survivors.…”

“…Studies should now focus on delineation of the goal of postischemic cognitive decline without dementia, which could be a preliminary stage of postischemic dementia and is much more frequent in clinical practice. Brain ischemia like Alzheimer's disease is a neuropathological condition accompanied by neuroinflammation and immune system changes [33,46,64,72]. One minute of brain ischemia is estimated to destroy approximately 2 million neurons and 14 million synapses [57].…”

“…Old age is associated with enhanced susceptibility to ischemic stroke and poor recovery from postischemic injury, but the cellular mechanisms which trigger these phenomena are only partially understood [30,46,[52][53][54]68,70]. Therefore, studying the complex processes underlying postischemic recovery of structural and cognitive functions in individuals a long time after birth is of considerable clinical importance [54].…”

“…In the wake of this neurodegenerative pathology, with limited medical therapies, alternative treatments are required which can control the progression of postischemic neurodegeneration. All the neurodegenerative diseases have common mechanisms of neuropathogenesis which include genetic alterations, protein and mitochondrial dysfunction, oxidative stress, cytokine changes and neuroinflammation [46,52,53]. Current research has shown that dietary polyphenols target the molecular changes of neurodegeneration with their ability to cross the blood-brain barrier as they control neuronal disease pathways at a molecular level by targeting these common features of neurodegeneration [14].…”